CircFhit Modulates GABAergic Synaptic Transmission via Regulating the Parental Gene Fhit Expression in the Spinal Dorsal Horn in a Rat Model of Neuropathic Pain.
10.1007/s12264-022-01014-5
- Author:
Ting XU
1
;
Zhen-Yu LI
1
;
Meng LIU
2
;
Su-Bo ZHANG
1
;
Huan-Huan DING
3
;
Jia-Yan WU
1
;
Su-Yan LIN
4
;
Jun LIU
5
;
Jia-You WEI
1
;
Xue-Qin ZHANG
6
;
Wen-Jun XIN
7
Author Information
1. Neuroscience Program of Zhongshan School of Medicine and the Fifth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China.
2. Department of Anesthesia and Pain Medicine, Guangzhou First People's Hospital, Guangzhou, 510000, China.
3. Department of Physiology, Xuzhou Medical University, Xuzhou, 221004, China.
4. Department of Neurology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510000, China. linsy33@mail2.sysu.edu.cn.
5. Department of Neurology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, 510000, China.
6. The Affiliated Brain Hospital (Guangzhou Huiai Hospital) and School of Health Management, Guangzhou Medical University, Guangzhou, 510182, China. gzzxq2005@126.com.
7. Neuroscience Program of Zhongshan School of Medicine and the Fifth Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. xinwj@mail.sysu.edu.cn.
- Publication Type:Journal Article
- Keywords:
Chronic pain;
CircRNA;
Epigenetic regulation;
Inhibitory transmission;
Neuropathic pain
- MeSH:
Rats;
Animals;
Posterior Horn Cells/pathology*;
Spinal Cord Dorsal Horn/metabolism*;
Neuralgia;
Synaptic Transmission
- From:
Neuroscience Bulletin
2023;39(6):947-961
- CountryChina
- Language:English
-
Abstract:
Effective treatments for neuropathic pain are lacking due to our limited understanding of the mechanisms. The circRNAs are mainly enriched in the central nervous system. However, their function in various physiological and pathological conditions have yet to be determined. Here, we identified circFhit, an exon-intron circRNA expressed in GABAergic neurons, which reduced the inhibitory synaptic transmission in the spinal dorsal horn to mediate spared nerve injury-induced neuropathic pain. Moreover, we found that circFhit decreased the expression of GAD65 and induced hyperexcitation in NK1R+ neurons by promoting the expression of its parental gene Fhit in cis. Mechanistically, circFhit was directly bound to the intronic region of Fhit, and formed a circFhit/HNRNPK complex to promote Pol II phosphorylation and H2B monoubiquitination by recruiting CDK9 and RNF40 to the Fhit intron. In summary, we revealed that the exon-intron circFhit contributes to GABAergic neuron-mediated NK1R+ neuronal hyperexcitation and neuropathic pain via regulating Fhit in cis.
